Method of treating COPD with artificial arterio-venous fistula and flow mediating systems

ABSTRACT

A method for treatment of COPD, hypertension, and left ventricular hypertrophy, and chronic hypoxia including creation of an artificial arterio-venous fistula and installation of a flow mediating device proximate the fistula. The flow mediating device is operated to limit flow as medically indicated to provide the optimum amount of bypass flow.

FIELD OF THE INVENTIONS

The inventions described below relate to treatments for pulmonaryhypertension and vascular surgery.

BACKGROUND OF THE INVENTIONS

Chronic obstructive pulmonary disease (COPD), chronic hypoxia,hypertension, and left ventricular hypertrophy and pulmonaryhypertension are diseases of the cardiopulmonary system. Chronicobstructive pulmonary disease (COPD), which includes chronic bronchitisand emphysema, is a slowly progressive lung disease caused primarily bysmoking. In COPD, the lungs are damaged and the airways are partlyobstructed, making it difficult to breath and leading to a gradual lossof lung function. Symptoms of COPD include chronic cough, excessivesputum production, low blood oxygen levels and severe disablingshortness of breath. COPD represents the fourth leading cause of deathin the United States. Chronic hypoxia (reduction of oxygen supply to thebody despite adequate blood flow through the body), hypertension, andleft ventricular hypertrophy are related conditions which may besymptomatic of COPD or coincident with COPD.

These serious conditions affect many people, and the primary treatmentsare merely ameliorative. The primary treatments for COPD includeavoidance of irritants such as tobacco smoke and breathing supplementaloxygen. In advanced cases of COPD, lung reduction surgery is sometimesperformed, but it is not clear that it helps. There is no known cure forCOPD.

An aortocaval fistula (ACF) is a rare clinical condition that can beeither spontaneous (80% of the cases), related to abdominal aorticaneurysm, or the result of some trauma such as lumbar disk surgery. Itis currently seen as a defect that should be cured with surgery and,possibly, stent-graft implantation in the aorta. Likewise,arterio-venous fistulas are uncommon, and can be caused by trauma or maybe iatrogenic (i.e.., an unintended result of vascular intervention, asdiscussed in Ruebben, et al., Arteriovenous fistulas induced by femoralarterial catheterization: percutaneous treatment, 209 Radiology, 729(1998)). Arteriovenous fistulas are also see as defects that should becured with surgery and, possibly, stent-graft implantation.

Contrary to this understanding, an intentionally formed aortocavalfistula appears to be a viable treatment for COPD. Recently, in ourco-pending U.S. patent application Ser. No. 10/820,169 (Attorney DocketNumber S03-013/US) filed Apr. 6, 2004, entitled ImplantableArteriovenous Shunt Device and listing John L. Faul, ToshihikoNishimura, Peter N. Kao & Ronald G. Pearl as inventors (the entirety ofwhich is hereby incorporated by reference), we propose creation of anartificial aortocaval fistula as a treatment for COPD, and we disclosethe method of creating the fistula and an implantable shunt formaintaining the aortocaval fistula. In our co-pending U.S. patentapplication Ser. No. 10/927,704 filed Aug. 27, 2004 (the entirety ofwhich is hereby incorporated by reference) we disclose a vascular shuntrivet which serves to hold contiguous points of the patient's aorta andinferior vena cava (or other arteries and their associated veins, suchas the femoral artery and femoral vein, or the carotid artery and thecarotid vein) together and maintain an open flow path from the aorta tothe vena cava. The device functions as a rivet, holding the two vesselwalls in close proximity, and as a shunt, permitting and maintainingflow from one blood vessel to the other as a treatment for COPD.

The method of treating COPD by creating an artificial arterio-venousfistula and maintaining the fistula with an endoprosthesis may beimproved with the addition of mechanisms for adjusting the arterialbypass flow rate to optimum levels. Adjustments to flow may be made tobalance the positive effects of injecting oxygenated blood into thevenous system with the potential negative effects.

SUMMARY

The devices and methods described below provide for treatment of COPD,hypertension, and left ventricular hypertrophy, and chronic hypoxia.After creation of an artificial arterio-venous fistula, a flow mediatingdevice is installed proximate the fistula (directly on the fistula,immediately upstream of the fistula in the artery, or immediatelydownstream of the fistula in the vein). In one embodiment of the method,a bladder is installed proximate the vein, artery or the fistula itself,and is inflated to impinge upon the vein, artery or the fistula to limitbypass flow through the fistula. Other mechanisms for controlling floware also proposed, including shunts (placed to maintain the fistula)having mechanisms for throttling flow through the shunt, and even priorart screw operated clamps for compressing some portion of the flow path.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the method of creating an artificial arterio-venousfistula and controlling flow with a balloon impinging on the artery.

FIG. 2 is a detail view of the inflatable cuff and its associatedcomponents, installed over the femoral vein of the patient.

FIG. 3 illustrates installation of the cuff over the left femoralartery.

FIGS. 4, 5 and 6 illustrate use of bladder which merely impinges on thefemoral vein to control bypass flow.

FIGS. 7 and 8 illustrate a bladder assembly which assists in operablycoupling the bladder to the blood vessel.

FIG. 9 shows the bladder assembly of FIG. 8 disposed in impingingrelationship with the anatomical fistula.

FIGS. 10 and 11 illustrate use of shunt with an integral bladder, whichmay be inflated to control flow through the shunt, as desired to affectthe arterial bypass flow as treatment for COPD.

FIGS. 12 and 13 illustrate another mechanism for regulating fistulabypass flow, in which a membranous wall of the shunt may be magneticallydrawn to control the size of the shunt lumen.

DETAILED DESCRIPTION OF THE INVENTIONS

FIG. 1 illustrates the method of creating an artificial arterio-venousfistula and controlling flow with a balloon impinging on the artery. Aportion of the vasculature of the patient 1 is shown, illustrating theleft and right femoral artery/external femoral arteries 3L and 3R, theleft and right common iliac arteries 4L and 4R, and the abdominal aorta5. Portions of the venous system are also illustrated the vena cava 6,which runs parallel to the aorta, and is typically contiguous with theaorta, the left and right femoral veins 9L and 9R. An artificialarterio-venous fistula or side-to-side anastomosis 7 may be formedbetween the femoral vein and femoral artery on either side of the body,indicated as items 10R and 10L, or between the iliac artery and thefemoral vein, and at locations within the aorta, as indicated at item 7.The artificial fistula may be maintained as an anatomical fistula,consisting of vascular tissue, if the local anatomy tends to heal to astable and patent fistula, or it may be maintained by shunt or shuntrivet 8 as illustrated, or by an endoprosthesis (a vascular graft orstent graft) of significant length.

To regulate flow through the fistula, an inflatable cuff 11 is placedand implanted around the femoral vein, proximal to the fistula (closerto the heart relative to the fistula). The inflatable cuff is furtherillustrated in FIG. 2, which shows the inflatable cuff assembly whichincludes the cuff 11, secured around the vein with suture seam 12, asubcutaneous injection port 13 with a resealable membrane 14, and ashort conduit 15 providing for fluid communication between the injectionport and the cuff (the injection port and resealable membrane may alsobe formed integrally with the cuff). The cuff may also be installed overthe femoral artery 3L, proximal to the fistula, as shown in FIG. 3.Inflation of the cuff results squeezing the blood vessel within thecuff, essentially throttling flow through the blood vessel. The degreeto which flow is mediated or throttled depends on the degree to whichthe cuff is inflated.

FIGS. 4, 5 and 6 illustrate use of bladder which merely impinges on thefemoral vein to control bypass flow. As shown in FIG. 4, a bladder isplaced in immediate contact with the femoral vein 9. The fistula 7 isshown in phantom, and may be fitted with a shunt or rivet 8. The bladder16 is an elongate bladder, which may be conformal or non-conformal,which is inflated through the associated access port 17. FIG. 5 shows across section of the leg, with the bladder uninflated, impinging on thefemoral vein, while FIG. 6 illustrates the effect of the inflatedbladder on the femoral vein. Upon inflation, the bladder furtherimpinges upon the femoral vein to impede flow, and thereby impede bypassflow from the femoral artery to the femoral vein.

FIGS. 7 and 8 illustrate a bladder assembly which assists in operablycoupling the bladder to the blood vessel, so that distention of thebladder is certain to result in impingement on the blood vessel. In FIG.7, the bladder 16 is coupled to a band 21 which provides an anvilagainst which the balloon pushes the blood vessel, and prevents theblood vessel from merely moving in response to balder inflation. Theband may be attached to the balloon at each end, as shown, or the bandmay be wrapped completely around both the bladder and the blood vessel.FIG. 8 illustrates another a bladder assembly which assists in operablycoupling the bladder 16 to the blood vessel, so that distention of thebladder is certain to result in impingement on the blood vessel. In thisfigure, a relatively hard and rigid clip 22 is hinged or otherwiserotatably attached to the balloon at hinge point 23, on one end or theother, and is fastened with the hook or other closure mechanism 24 atthe other, so that the bladder may be fastened to the blood vessel. Theclip is narrow and elongate, so that it may be used as shown in FIG. 9,with the bladder 16 disposed in impinging relationship with theanatomical fistula 25 and the clip disposed on the opposite side of thefistula and closed upon the bladder or an extending structure (in thiscase, the conduit used to fill the bladder). If a graft of significantlength is used, the devices of FIGS. 7, 8 and 9 may be placed overcontiguous parallel segments of the shunt and artery, or the shunt andthe vein.

Any other adjustable vascular impingement device may be used, includingthe Flow-watch® pulmonary artery band system which includes a jack screwadjusted by a motor which is powered and controlled telemetrically, asdescribed in Stergiopulis, Flow Control Device and Method, PCT App.PCT/EP00/06907 (Jan. 25, 2001), or screw operated bands such as thosedisclosed in Schlensak, et al., Pulmonary Artery Banding With A NovelPercutaneously, Bidirectionally Adjustable Device, 12 Eur. J. ofCardio-thoracic Surg. 931-933 (1997).

The devices and methods described above may be used to treat COPD asfollows. First, a surgeon creates a fistula between an artery and anearby vein. Preferably, the artery and vein are large, such as thefemoral artery and the femoral artery. The fistula may be maintained,after artificial creation, either naturally to create an anatomicalfistula comprising portions of the contiguous artery and vein healedtogether, or it may be a mechanically maintained fistula which issupported with a shunt or stent, or it may comprise a distinct shuntfrom the artery to the vein. After creating and stabilizing the fistula(ensuring that endoprosthesis are securely implanted, or that theanatomical fistula is structurally sound), the surgeon implants the flowrestricting device (which may be any one of the devices described ormentioned herein) around the vein downstream from the fistula, or aroundthe artery upstream from the fistula, or across the fistula itself. Tocontrol flow through the fistula, the cuff is inflated or deflated asnecessary to achieve a desired bypass flow volume. The desired by-passflow volume is determined by monitoring blood oxygenation and cardiacfunction intra-operatively (that is, immediately after creation of thefistula and implantation of the flow restricting device) and/or (thatis, before discharge) and adjusting bypass flow to obtain a medicallyindicated short-term change in such parameters. The desired by-pass flowshould also be determined and adjusted post-operatively, after astabilization period (a few weeks after surgery). The shunt willincrease mixed venous oxygenation, (SvO2), increase the percentage ofoxygen bound to hemoglobin (SpO2), increase the amount of oxygendissolved in blood plasma (PaO2), and increase cardiac output and strokevolume (after remodeling). Initially (immediately after opening theshunt) the heart rate increases to provide increased cardiac output.Then, as the heart ‘remodels’ the stroke volume increases and the heartrate comes back down to normal levels to maintain increased cardiacoutput. Lower bypass flow in the post-operative and stabilization timeperiod may be desirable to avoid over stressing the heart and allow amore gradual cardiac re-modeling. Thus, the overall procedure may beaccomplished by adjusting flow in the peri-operative and stabilizationtime frame to levels sufficient to increase PaO₂ and/or SvO₂ about 5% ormore, and increase cardiac output by about 10% or more, followed byre-evaluation of the patient after stabilization and readjustment ofby-pass flow to provide for an increase PaO₂ and/or SvO₂ (relative topre-operative levels) of about 10% to 20% or more, depending on patienttolerance. Should the heart rate increase attendant to the bypass flowbe more tolerable, the bypass flow in the peri-operative andstabilization time frame may adjusted to higher levels, to provide foran increase in PaO₂ and/or SvO₂ of about 20% to 25% (for a COPD with lowPaO₂ and/or SvO₂), followed by re-evaluation of the patient afterstabilization (after long-term remodeling of the heart, the heart may beremodeled in response to the therapy) and reduction of by-pass flow toprovide for an increase PaO₂ and/or SvO₂ (relative to pre-operativelevels) by about 10% to 20%. The optimal levels of these parameters, andthe optimum trade-off between increased blood levels, cardiac output andincreased heart rate are expected to be refined with clinicalexperience.

Rather than impinging on the blood vessel as described above, thedesired flow control may be achieved by providing a shunt with avariable lumen cross-section or other flow control means which may actas a throttle valve. FIGS. 10 and 11 illustrate use of shunt with anintegral bladder which may be inflated to control flow through theshunt, as desired to effect the arterial bypass flow as treatment forCOPD. A shunt 26 is installed between the femoral artery and the femoralvein. The shunt additionally comprises a bladder 27 installed within thelumen of the shunt, which is filled as desired through the inflationport 28. As illustrated in FIG. 11, in which the bladder is partiallyinflated, the bladder partially occludes the shunt, to a degreedependent on the degree to which the bladder is inflated. The bladdermay be fully inflated to fully occlude the shunt and prevent bypassflow. The shunt may be made of any suitable shunt material.

FIGS. 12 and 13 illustrate another mechanism for regulating fistulabypass flow, in which a membranous wall of the shunt may be magneticallydrawn to control the size of the shunt lumen. In this embodiment, theshunt is provided with an rigid outer wall 29 and flexible inner wall30. The dissectible portion of the inner wall which cuts across thelumen may be elastic or merely loose, so that it may be pulled againstthe outer wall to fully open the lumen. A magnet (or ferromagnetic mass)31 is fixed to the dissectible portion of the inner wall, such that themagnet, and thus the dissectible portion of the inner wall, may be drawnagainst the outer by magnetic attraction to an extracorporeal magnet 32.The extracorporeal magnet may be an electromagnet with operatingcircuitry which is fixed to the patient in proximity to the shunt, or itmay be a permanent magnet, the power of which may be selected to effecta desired degree of openness.

While the devices and methods have been described relative to thefemoral artery and femoral vein, they may also be employed in othersuitable contiguous or associated artery/vein pairs, including the aortaand inferior vena cava, the femoral vein and the iliopopliteal vein oriliac vein, the popliteal artery and popliteal vein, the carotid arteryand the jugular vein, the brachial artery and brachial vein, thebrachial artery and brachial vein, and the brachio-cephallic artery andsubclavian vein. The artery-to-vein shunt may also be provided betweenremote anastomosis cites, such as the iliac artery to the inferior venacava. Also, though discussed in terms of COPD treatment, the methodshould be useful to treat hypertension (pulmonary hypertension andarterial hypertension), left ventricular hypertrophy, and chronichypoxia. Thus, while the preferred embodiments of the devices andmethods have been described in reference to the environment in whichthey were developed, they are merely illustrative of the principles ofthe inventions. Other embodiments and configurations may be devisedwithout departing from the spirit of the inventions and the scope of theappended claims.

1. A method of treating COPD in a patient, said method comprising thesteps of: creating an artificial fistula between an artery and a vein ofthe patient; installing a flow mediating device proximate the artificialfistula; operating the flow-mediating device to control bypass bloodflow through the fistula as indicated to treat COPD.
 2. The method ofclaim 1 further comprising: operating the flow-mediating device tocontrol bypass blood flow through the fistula to achieve an increase inthe patient's PaO₂ by at least about 5% as indicated to treat COPD. 3.The method of claim 1 further comprising: operating the flow-mediatingdevice to control bypass blood flow through the fistula to achieve anincrease in the patient's SvO₂ by at least about 5% as indicated totreat COPD.
 4. The method of claim 1 further comprising: operating theflow-mediating device to control bypass blood flow through the fistulato achieve an increase in the patient's cardiac output by at least about10% as indicated to treat COPD.
 5. The method of claim 1 furthercomprising: evaluating the patient after a stabilization period andadjusting the flow mediating device to control bypass blood flow throughthe fistula to achieve an increase in the patient's cardiac output by atleast about 10%.
 6. The method of claim 1 further comprising: providingthe flow control device in the form of an inflatable bladder systemcomprising an inflatable cuff adapted to substantially surround aportion of the patient's vasculature proximate the fistula and means fordelivering fluid to the inflatable cuff.
 7. The method of claim 1further comprising: providing the flow control device in the form of aninflatable bladder adapted to impinge upon a portion of the patient'svasculature proximate the fistula and means for delivering fluid to theinflatable bladder.
 8. The method of claim 1 further comprising thesteps: of providing a band adapted to surround a vessel of the patientsvasculature and securing the bladder to the patients vasculature withthe band, proximate the fistula.
 9. The method of claim 1 furthercomprising: providing the flow control device in the form of aninflatable bladder adapted to impinge upon a portion of the patient'svasculature proximate the fistula, rigid fastener operably connected tothe bladder and means for delivering fluid to the inflatable bladder;and installing the bladder against a portion of the patient'svasculature proximate the fistula and securing the bladder against theportion of the patient's vasculature by placing a portion of the rigidfastener opposite the bladder with the portion of the patient'svasculature disposed between the bladder and the clip, and securing therigid fastener to the bladder.
 10. The method of claim 1 furthercomprising: providing the flow control device in the form of a shunt orgraft between an artery and a nearby vein, and providing throttlingmeans operable to mediate flow through the shunt of graft.
 11. Themethod of claim 10 further comprising: providing the throttling means inthe form of a shunt or graft having a lumen and a bladder disposedwithin the lumen, and inflating the bladder as desired to changedocclude the lumen to the degree necessary to obtain desired bypass flow.12. The method of claim 10 further comprising: providing the throttlingmeans in the form of a shunt or graft having a lumen and an dissectiblewall portion within the lumen, a magnetic mass fixed to the dissectiblewall portion, said magnetic mass being operable to deflect thedissectible wall portion when acted upon by a magnet.
 13. The method ofclaim 10 further comprising: providing the throttling means in the formof a shunt or graft having a lumen and compliant sidewalls and a piston212/637 disposed outside the shunt or graft and means for driving thepiston against the sidewall of the shunt or graft to squeeze the shuntor graft to change the size of the lumen; and operating the piston tosqueeze or release the shunt or graft as desired to mediate flow throughthe shunt or graft.
 14. The method of claim 1 further comprising:placing the flow mediating device on the vein downstream from thefistula.
 15. The method of claim 1 further comprising: placing the flowmediating device on the artery upstream from the fistula.
 16. The methodof claim 1 further comprising: placing the flow mediating devicedirectly over the fistula.
 17. The method of claim 1 further comprising:creating the artificial fistula between a femoral artery and femoralvein of the patient.
 18. The method of claim 1 further comprising:creating the artificial fistula between one of the following vein/arterypairs: the aorta and inferior vena cava, the femoral vein and theiliopopliteal vein or iliac vein, the carotid artery and the carotidvein or jugular vein, the brachial artery and brachial vein, and thebrachio-cephallic artery and subclavian vein.